长链非编码RNA遗传变异与膀胱癌发病风险及其分子机制探讨

项目名称： 长链非编码RNA遗传变异与膀胱癌发病风险及其分子机制探讨

项目编号： No.81473050

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张正东

作者单位： 南京医科大学

项目金额： 85万元

中文摘要： 长链非编码RNA（lncRNA）是长度超200个核苷酸的非编码功能性RNA，参与肿瘤发生发展，其遗传变异也与肿瘤发病风险密切关联，但确切机制尚不清楚。本课题组前期基于文献报道并经膀胱癌组织验证，筛选出5个差异表达lncRNAs（H19、SNHG16、UCA1、MEG3和PTENP1），提示其参与膀胱癌发生。本项目基于前期预研结果，拟运用病例-对照方法和标签SNPs策略，探讨5个候选lncRNAs基因遗传变异与膀胱癌发病风险的关系，并分析基因-基因、基因-环境交互作用及基因型-临床表型关系；进而采用分子生物学方法，探讨SNPs对lncRNAs功能学影响及其机制；最后，检测血浆lncRNAs表达水平，初步评估其作为膀胱癌生物标志物的价值。本研究为揭示lncRNAs在膀胱癌发生发展中的作用及其机制提供理论依据，并通过筛选潜在生物标志物，为膀胱癌易感人群筛查及个体化预防，早期诊断及治疗等提供参考。

中文关键词： 膀胱癌；长链非编码RNA；遗传变异；易感性；分子机制

英文摘要： Long noncoding RNAs (lncRNAs) is widely defined as functional RNA longer than 200 nucleotides, without protein-coding capability. lncRNAs play a vital role in cancer occurrence and development. Genetic variants in lncRNAs also have been shown to be associated with susceptibility of cancer, while the detailed mechanism was still unclear. Previously, we have detected expression levels of cancer-related lncRNAs in bladder cancer (BC) tissues and found 5 lncRNAs were differently expressed in BC (i.e. H19, SNHG16, UCA1, MEG3 and PTENP1), suggesting that they may participate in carcinogenesis of BC. Based on the previous results, we plan to use case-control studies to assess the association between selected tagSNPs in the 5 lncRNAs and BC risk in our present study, as well as detect the potential interactions between gene-gene and gene-environment and analyze the relationship of genotype-clinical phenotype. Furthermore, we will also conduct some molecular biology assays to investigate effects of the associated SNPs on functions of lncRNAs and the underlying mechanism. Finally, we will detect expression levels of lncRNAs in plasma and evaluate practical value of lncRNAs as potential biomarkers of BC. This project will provide theoretical basis for the role of lncRNA in carcinogenesis of BC, and contribute to screening of susceptible population, individualized prevention, early diagnoses and treatment of BC.

英文关键词： bladder cancer;long noncoding RNA;genetic variants;susceptibility;molecular mechanism